Lynn S. Ripley

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A model is described for the templated production of frameshift and base-substitution mutations mediated through aberrant DNA structures arising as a consequence of quasi-palindromic DNA sequences. Two general mechanisms are considered. One evokes the formation and processing of imperfect DNA secondary structures (hairpins) for the production of mutations.(More)
A model is presented for deletion mutations whose formation is mediated by palindromic and quasipalindromic DNA sequences. It proposes that the self-complementarity of palindromes allows the formation of DNA secondary structures that serve as deletion intermediates. The structures juxtapose the end points of the deletion and thus direct deletion(More)
The replication of premutagenic DNA lesions generates mutant progeny in patterns that distinguish lesions that rarely produce a mutation per DNA replication from those that frequently do so. The quantitative aspects of this distinction were tested in studies of heat-mutagenized bacteriophage T4. Previous T4 studies had demonstrated that transition mutations(More)
The in vivo production of frameshift and base-substitution mutations predicted as a consequence of the metabolic processing of misaligned quasipalindromic DNA sequences has been confirmed. Spontaneous frameshift mutations of the T4 rII gene that had been genetically mapped to quasipalindromic DNA sequences were sequenced. Some of the mutant sequences are(More)
Spontaneous mutations are rare and are produced by multiple biochemical mechanisms. Nonetheless, studies of these mechanisms have revealed striking examples in which mutational specificity can be regularly related to a characteristic of the surrounding DNA sequence and/or the enzymes participating in mutagenesis. Thus, to an increasing degree the DNA(More)
The sequences of more than 600 frameshift mutations produced as a consequence of in vitro DNA replication on an oligonucleotide-primed, single-stranded DNA template by the Escherichia coli polymerase I enzyme (PolI) or its large fragment derivative (PolLF) were compared. Four categories of mutants were found: (1) single-base deletions, (2) base(More)
In vitro, misalignments of the newly synthesized (primer) strand during DNA polymerization lead to deletion and/or complex frameshift mutations. In vivo, similar misalignments of repeated and quasipalindromic DNA sequences are predicted to be intermediates of mutagenesis. The mutagenic misalignments are mediated by complementary pairing between the sequence(More)
Heat induces transversions (as well as transitions) at G-C base pairs in bacteriophage T4. The target base for transversions is guanine,which is converted to a product which is sometimes replicated and transcribed as a pyrimidine.A model for this process is proposed in which the deoxyguanosine glycosidic bond migrates from N9 to N2: the resulting(More)